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1.
J Plast Reconstr Aesthet Surg ; 93: 62-69, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38663166

RESUMEN

INTRODUCTION: The EAR-Q is a rigorously validated patient-reported outcome measure, which evaluates ear appearance and health-related quality of life (HRQL) in patients with congenital or acquired ear conditions. The aim of this study was to conduct an exploratory analysis to examine the factors associated with EAR-Q appearance and HRQL scale scores. METHODS: In this study, 862 participants, aged 8-29 years, with congenital or acquired ear conditions, completed the EAR-Q as part of an international field-test study. Patients responded to demographic and clinical questions as well as the EAR-Q. Univariable and multivariable linear regression analyses were used to determine factors that were significant predictors for the scores on the EAR-Q Appearance, Psychological, and Social scales. RESULTS: Most participants were men (57.4%), awaiting treatment (55.0%), and had a microtia diagnosis (70.4%), with a mean age of 13 (±4) years. Worse ear appearance scores (p < 0.02) were associated with male gender, microtia, no history of treatment, ear surgery within 6 months, unilateral involvement, and greater self-reported ear asymmetry. Decreased psychological scores (p < 0.01) were associated with increasing participant age, no treatment history, recent ear surgery, and dissatisfaction with ears matching or overall dissatisfaction. Lower social scores (p ≤ 0.04) were associated with no treatment history, those awaiting surgery, ear surgery within the last 6 months, bilateral involvement, and self-reported ears matching or overall appearance. CONCLUSION: This analysis identified patient factors that may influence ear appearance and HRQL scale scores. These findings provide evidence of patient factors that should be adjusted for when undertaking future observational research designs using the EAR-Q in this patient population.

2.
Adv Sci (Weinh) ; 11(5): e2303495, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38037850

RESUMEN

Sodium aescinate (SA) shows great potential for treating lymphedema since it can regulate the expression of cytokines in M1 macrophages, however, it is commonly administered intravenously in clinical practice and often accompanied by severe toxic side effects and short metabolic cycles. Herein, SA-loaded chiral supramolecular hydrogels are prepared to prove the curative effects of SA on lymphedema and enhance its safety and transdermal transmission efficiency. In vitro studies demonstrate that SA- loaded chiral supramolecular hydrogels can modulate local immune responses by inhibiting M1 macrophage polarization. Typically, these chiral hydrogels can significantly increase the permeability of SA with good biocompatibility due to the high enantioselectivity between chiral gelators and stratum corneum and L-type hydrogels are found to have preferable drug penetration over D-type hydrogels. In vivo studies show that topical delivery of SA via chiral hydrogels results in dramatic therapeutic effects on lymphedema. Specifically, it can downregulate the level of inflammatory cytokines, reduce the development of fibrosis, and promote the regeneration of lymphatic vessels. This study initiates the use of SA for lymphedema treatment and for the creation of an effective chiral biological platform for improved topical administration.


Asunto(s)
Hidrogeles , Macrófagos , Saponinas , Triterpenos , Administración Cutánea , Citocinas
3.
Laryngoscope ; 134(1): 148-153, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37243347

RESUMEN

Hearing improvement is another basic requirement for microtia patients in addition to aesthetic needs. This quantitative framework fabrication method can reduce the learning curve, obtain satisfactory aesthetic results with few complications, and reserve a certain space for future canalplasty. Laryngoscope, 134:148-153, 2024.


Asunto(s)
Microtia Congénita , Cartílago Costal , Procedimientos de Cirugía Plástica , Humanos , Cartílago Costal/trasplante , Oído Externo/cirugía , Microtia Congénita/cirugía , Cartílago/trasplante
4.
Plast Reconstr Surg ; 153(4): 905-913, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37184475

RESUMEN

BACKGROUND: The EarWell System offers a correction opportunity for infants born with ear anomalies. However, the long-term effectiveness of ear molding remains unclear. This study aimed to explore the long-term effectiveness of this novel technique and to determine the risk factors for recurrence. METHODS: This retrospective, population-based cohort study was performed from 2017 through 2021. Infants who completed ear molding therapy and were followed up for longer than 6 months were enrolled. The main outcomes were immediate and long-term efficacy, which were graded by two blinded plastic surgeons. RESULTS: A total of 226 infants (334 ears) were recruited. The most common anomalies were helical deformities [113 ears (33.8%)], and the rarest were cryptotia [five ears (1.5%)] and conchal crus [five ears (1.5%)]. The age at initiation of treatment was a factor affecting both immediate ( P = 0.004) and long-term effectiveness ( P = 0.009). The type of anomaly also influenced long-term molding outcomes. For cup ears, the success rate of long-term outcomes (76.0%) was significantly lower than that of immediate outcomes (98.7%) ( P < 0.001). Prominent ear, cup ear, and microtia were found to be the most likely to relapse during long-term follow-up. The results of logistic regression also demonstrated age, duration time, and the type of anomaly to be risk factors of ear molding effects. CONCLUSIONS: The EarWell System was shown to be a secure and effective method for treatment of congenital ear anomalies. Some infants' ear anomalies recurred after successful immediate results. The age at initiation of treatment and the type of anomaly were predictors of long-term outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Asunto(s)
Pabellón Auricular , Procedimientos de Cirugía Plástica , Lactante , Humanos , Oído Externo/cirugía , Oído Externo/anomalías , Estudios Retrospectivos , Estudios de Cohortes , Pabellón Auricular/cirugía , Pabellón Auricular/anomalías , Resultado del Tratamiento
5.
J Sci Food Agric ; 103(15): 7469-7483, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37421609

RESUMEN

BACKGROUND: To determine how abscisic acid (ABA) affects tomato fruit ripening at the protein level, mature green cherry tomato fruit were treated with ABA, nordihydroguaiaretic acid (NDGA) or sterile water (control, CK). The proteomes of treated fruit were analyzed and quantified using tandem mass tags (TMTs) at 7 days after treatment, and the gene transcription abundances of differently expressed proteins (DEPs) were validated with quantitative real-time polymerase chain reaction. RESULTS: Postharvest tomato fruit underwent faster color transformation and ripening than the CK when treated with ABA. In total, 6310 proteins were identified among the CK and treatment groups, of which 5359 were quantified. Using a change threshold of 1.2 or 0.83 times, 1081 DEPs were identified. Among them, 127 were upregulated and 127 were downregulated in the ABA versus CK comparison group. According to KEGG and protein-protein interaction network analyses, the ABA-regulated DEPs were primarily concentrated in the photosynthesis system and sugar metabolism pathways, and 102 DEPs associated with phytohormones biosynthesis and signal transduction, pigment synthesis and metabolism, cell wall metabolism, photosynthesis, redox reactions, allergens and defense responses were identified in the ABA versus CK and NDGA versus CK comparison groups. CONCLUSION: ABA affects tomato fruit ripening at the protein level to some extent. The results of this study provided comprehensive insights and data for further research on the regulatory mechanism of ABA in tomato fruit ripening. © 2023 Society of Chemical Industry.


Asunto(s)
Ácido Abscísico , Solanum lycopersicum , Ácido Abscísico/farmacología , Ácido Abscísico/metabolismo , Solanum lycopersicum/genética , Frutas/metabolismo , Proteómica , Reguladores del Crecimiento de las Plantas/farmacología , Reguladores del Crecimiento de las Plantas/metabolismo , Masoprocol/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
6.
Burns Trauma ; 11: tkad019, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37476580

RESUMEN

Background: Several surgeons have described studies of free-tissue transfers using veins instead of arteries. These innovative microsurgical techniques can offer several advantages, such as an easier dissection during flap harvesting, and represent an alternative during an accidental surgical mistake or development of new surgical procedures. The purpose of this study was to describe and explore different constructs of vascularized lymph node transfer (VLNT) only based on venous blood flow in a mouse model, evaluate their blood flow microcirculation through indocyanine green (ICG) angiography and investigate the lymphatic drainage function and the lymph nodes' structures. Methods: Five types of venous lymph node flaps (LNF) were created and investigated: Types IA, IB, IC, IIA and IIB were developed by ICG intraoperatively (with videos in the article). Seven weeks later, by applying methylene blue, the recanalization of the lymphatic vessels between the LNF and the recipient site was detected. Lymph nodes were collected at the same time and their structures were analyzed by hematoxylin and eosin staining analysis. Results: All of the venous LNFs developed except Type IC. Seven weeks later, methylene blue flowed into Types IA, IB, IIA and IIB from recipient sites. When comparing with arteriovenous lymph node, the medullary sinus was diffusely distributed in venous lymph nodes. The proportion of cells was significantly reduced (p < 0.05). The artery diameters were significantly smaller (p < 0.05). The veins diameters and lymphatic vessels output in Types IA, IB, IIA and IIB were more dilated (p < 0.05). Conclusions: This research demonstrated that Type IA, IB, IIA and IIB venous LNFs can retrogradely receive venous blood supply; they can survive, produce a lymphatic recanalization and integrate with the surrounding tissue, despite lymph node structural changes. Our results will improve the understanding of the survival mechanism of venous LNFs and will help researchers to design new studies or lymphatic models and eventually find an alternative procedure for the surgical treatment of lymphedema.

7.
Foods ; 12(12)2023 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-37372568

RESUMEN

SlAREB1, a member of the abscisic acid (ABA) response element-binding factors (AREB/ABFs) family, was reported to play a crucial role in the expression of ABA-regulated downstream genes and affect the ripening of tomato fruit. However, the downstream genes of SlAREB1 are still unclear. Chromatin immunoprecipitation (ChIP) is a powerful tool and a standard method for studying the interactions between DNA and proteins at the genome-wide level. In the present study, SlAREB1 was proved to continually increase until the mature green stage and then decrease during the ripening period, and a total of 972 gene peaks were identified downstream of SlAREB1 by ChIP-seq analysis, mainly located in the intergenic and promoter regions. Further gene ontology (GO) annotation analysis revealed that the target sequence of SlAREB1 was the most involved in biological function. Kyoto Encylopaedia of Genes and Genomes (KEGG) pathway analysis showed that the identified genes were mainly involved in the oxidative phosphorylation and photosynthesis pathways, and some of them were associated with tomato phytohormone synthesis, the cell wall, pigment, and the antioxidant characteristic of the fruit as well. Based on these results, an initial model of SlAREB1 regulation on tomato fruit ripening was constructed, which provided a theoretical basis for further exploring the effects of the regulation mechanism of SlAREB1 and ABA on tomato fruit ripening.

8.
Wound Repair Regen ; 31(3): 360-366, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36751728

RESUMEN

The venous lymph node flap (vLNF) is regarded as an arterialized or 'pure' venous flap, subject to which type of vessel provides blood supply to the flap. However, whether the vLNF drainage function is maintainable or sufficient for the treatment of lymphoedema is yet to be elucidated. In this study, the venous flow-through lymph node flaps or 'pure' vLNF was investigated in a rat's tail (lymphoedema model), and the therapeutic effect was analysed to clarify its potential value for the treatment of lymphoedema. The subjects (rats) were divided into three groups, the experimental group ('pure' vLNF group), the control group (lymphoedema group), and the baseline group. The tail circumference and diameter were recorded for 5 weeks after the operation. Five weeks after surgery, the lymphatic drainage function was evaluated using indocyanine green (ICG) lymphography, while the skin thickness and collagen layer were assessed by histological analysis. The average diameter and circumference of the experimental group were significantly shorter than the control group (p < 0.01). When comparing ICG lymphography within the three groups, the baseline group showed that the ICG entered the inguinal lymph node and appeared in the liver while the ICG still accumulated in the oedematous tail with no fluorescence emerging in other parts of the rat's body, in the control group. In the experimental group, the ICG entered the vLNF via the flap junction with the rat's tail and fluorescence emerging in the rat's liver. When comparing the three groups above with the control group, the experimental group's skin and collagen layer thickness were significantly improved (p < 0.01). Lymphatic recanalization was shown to appear between 'pure' vLNF and the recipient area. Moreover, vLNF was shown to drain lymph fluid via the venous system, thus relieved swelling and fibrosis of the lymphoedematous tissue. Consequently, this could represent a new potential surgical approach for the treatment of lymphoedema.


Asunto(s)
Linfedema , Cicatrización de Heridas , Ratas , Animales , Ganglios Linfáticos , Linfedema/cirugía , Colgajos Quirúrgicos/irrigación sanguínea , Linfografía , Verde de Indocianina/farmacología
9.
Acad Radiol ; 30(11): 2458-2468, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36586760

RESUMEN

RATIONALE AND OBJECTIVES: Preoperative prediction of LVI status can facilitate personalized therapeutic planning. This study aims to investigate the efficacy of preoperative MRI-based radiomics for predicting lymphatic vessel invasion (LVI) determined by D2-40 in patients with invasive breast cancer. MATERIALS AND METHODS: A total of 203 patients with pathologically confirmed invasive breast cancer, who underwent preoperative breast MRI, were retrospectively enrolled and randomly assigned to the following cohorts: training cohort (n=141) and test cohort (n=62). Then, univariate and multivariate logistic regression were performed to select independent risk factors and build a clinical model. Afterwards, least absolute shrinkage and selection operator (LASSO) logistic regression was performed to select predictive features extracted from the early and delay enhancement dynamic contrast-enhanced (DCE)-MRI images, and a radiomics signature was established. Subsequently, a nomogram model was constructed by incorporating the radiomics score and risk factors. Receiver operating characteristic curves were performed to determine the performance of various models. The efficacy of the various models was evaluated using calibration and decision curves. RESULTS: Fourteen radiomics features were selected to construct the radiomics model. The size of the lymph node was identified as an independent risk factor of the clinical model. The nomogram model demonstrated the best calibration and discrimination performance in both the training and test cohorts, with an area under the curve of 0.873 (95% confidence interval [CI]: 0.807-0.923) and 0.902 (95% CI: 0.800-0.963), respectively. The decision curve illustrated that the nomogram model added more net benefits, when compared to the radiomics signature and clinical model. CONCLUSION: The nomogram model based on preoperative DCE-MRI images exhibits satisfactory efficacy for the noninvasive prediction of LVI determined by D2-40 in invasive breast cancer.

10.
BMC Neurol ; 22(1): 498, 2022 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-36550486

RESUMEN

PURPOSE: The MRI features of Diffuse midline glioma, H3 K27-altered and glioma in the midline without H3 K27-altered were compared and analyzed, and the changes in the apparent diffusion coefficient (ADC) of the two groups were quantitatively analyzed. METHODS: The MRI images of 35 patients with Diffuse midline gliomas, H3 K27-altered and gliomas in the midline without H3 K27-altered were analyzed retrospectively. The location, edge, signal, peritumoral edema and enhancement characteristics of the lesions were observed, and the changes in ADC values were analyzed. RESULTS: In the H3 K27-altered group, 85.7% (12/14) of the tumors were located in the thalamus and brainstem compared with 28.6% (6/21) in the no H3 K27-altered group. In the H3 K27-altered group, for tumors only located in the midline area, only 14.3% (1/7) had irregular shapes and unclear boundaries, while for tumors also invaded the extramidline tissues 85.7% (6/7) had irregular shapes and unclear boundaries.The"basilar artery wrapped sign" was found in 6 patients with tumors located in the pons in the H3 K27-altered group, but none in the no H3 K27-altered group had this sign. In the H3 K27-altered group, only 14.3% (1/7) of the tumors confined to the midline area had small cystic degeneration and necrosis, while for tumors also invaded the extramidline tissues, 100% (7/7) of the tumors had cystic degeneration and necrosis, and the cystic degeneration and necrosis only located in the extramidline region of the tumor in 6 cases.A total of 78.6% (11/14) of tumors in the H3 K27-altered group showed mild to moderate enhancement, while 47.6% (10/21) of tumors in the no H3 K27-altered group showed mild to moderate enhancement. The average peritumoral edema index was 1.13 in the H3 K27-altered group and 1.75 in the no H3 K27-altered group. The average ADC value of tumor in the H3 K27-altered group was 7.83 × 10- 4 mm2/s, and the ratio to normal brain tissue was 0.844, while the values in the no H3 K27-altered group were 13.5 × 10- 4 mm2/s and 1.75, respectively. CONCLUSION: Compared with gliomas in the midline without H3 K27-altered, The MRI findings and ADC value of Diffuse midline gliomas, H3K27-altered have some characteristics, which can help improve the diagnosis and differential diagnosis.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/patología , Histonas/genética , Estudios Retrospectivos , Mutación , Glioma/diagnóstico por imagen , Glioma/patología , Imagen por Resonancia Magnética
11.
J Clin Pharm Ther ; 47(10): 1563-1569, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35670240

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Only a few studies about polymyxin B (PMB) against multidrug-resistant gram-negative bacteria (MDR GNB) infection were conducted in liver transplantation recipients (LTRs). The purpose of this study was to investigate the efficacy and safety of PMB in the treatment of MDR-GNB in liver transplant recipients and to determine the risk factors affecting clinical cure and 30-day all-cause mortality. METHODS: Data of LTRs receiving PMB from January 2016 to February 2020 were collected. Clinical cure and 30-day all-cause mortality were the main efficacy outcomes, while the incidence of nephrotoxicity, neurotoxicity, and hyperpigmentation of PMB was the main safety outcome. RESULTS AND DISCUSSION: Data of 42 LTRs were included. Clinical cure with PMB was observed in 27 recipients (64.3%), and the 30-day all-cause mortality rate was 31.0% (13/42). The incidence of acute kidney injury (AKI), neurotoxicity, and hyperpigmentation was 57.1% (16/28), 4.8% (2/42), and 16.7% (7/42), respectively. Logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation (APACHE) II score (OR, 1.203; 95% CI, 1.016-1.423, p = 0.032) was an independent risk factor for 30-day all-cause mortality, whereas renal replacement therapy (OR, 0.128; 95% CI, 0.019-0.860, p = 0.034) was an independent risk factor for clinical cure with PMB. WHAT IS NEW AND CONCLUSIONS: This is the first study to evaluate the application of PMB in LTRs. If there were no better therapeutic options left for LTRs other than PMB, it can be used against MDR GNB infection in LTRs. We should closely observe adverse events or reactions, and adjust the dose based on the balance of efficacy and safety.


Asunto(s)
Lesión Renal Aguda , Infecciones por Bacterias Gramnegativas , Hiperpigmentación , Trasplante de Hígado , Lesión Renal Aguda/inducido químicamente , Antibacterianos/efectos adversos , Bacterias Gramnegativas , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Hiperpigmentación/inducido químicamente , Trasplante de Hígado/efectos adversos , Polimixina B/efectos adversos
12.
J Magn Reson Imaging ; 55(3): 772-784, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34453461

RESUMEN

BACKGROUND: Evaluating tumor-infiltrating lymphocytes (TILs) in patients with breast cancer using radiomics has been rarely explored. PURPOSE: To establish a radiomics nomogram based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for preoperatively evaluating TIL level. STUDY TYPE: Retrospective. POPULATION: A total of 154 patients with breast cancer were divided into a training cohort (N = 87) and a test cohort (N = 67), who were further divided into low TIL (<50%) and high TIL (≥50%) subgroups according to the histopathological results. FIELD STRENGTH/SEQUENCE: 3.0 T; axial T2-weighted imaging (fast spin echo), diffusion-weighted imaging (spin echo-echo planar imaging), and the volume imaging for breast assessment DCE sequence (gradient recalled echo). ASSESSMENT: A radiomics signature was developed from the training dataset and independent risk factors were selected by multivariate logistic regression to build a clinical model. A nomogram model was built by combining radiomics score and risk factors. The performance of the nomogram was assessed using calibration curves and decision curves. The area under the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were calculated. STATISTICAL TESTS: The least absolute shrinkage and selection operator, univariate and multivariate logistic regression analysis, t-tests and chi-squared tests or Fisher's exact test, Hosmer-Lemeshow test, ROC analysis, and decision curve analysis were conducted. P < 0.05 was considered statistically significant. RESULTS: The radiomics signature and nomogram model exhibited better calibration and validation performance in the training (radiomics: area under the curve [AUC] 0.86; nomogram: AUC 0.88) and test (radiomics: AUC 0.83; nomogram: AUC 0.84) datasets compared with clinical model (training: AUC 0.76; test: AUC 0.72). The decision curve demonstrated that the nomogram model exhibited better performance than the clinical model, with a threshold probability between 0.15 and 0.9. DATA CONCLUSION: The nomogram model based on preoperative MRI exhibited an excellent ability for the noninvasive evaluation of TILs in breast cancer. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 2.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Femenino , Humanos , Linfocitos Infiltrantes de Tumor , Imagen por Resonancia Magnética/métodos , Nomogramas , Estudios Retrospectivos
13.
Lymphat Res Biol ; 20(2): 164-174, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34028298

RESUMEN

Background: Gynecological cancer-related lymphedema (GCRL) is a devastating condition that adversely influences function, health, and quality of life. We conducted a randomized-controlled clinical study as well as in vitro experiments to investigate the efficacy and safety of far infrared radiation (FIR) to treat lymphedema in patients having previously undergone surgery for gynecological tumors. Materials and Methods: Seventy-four women with GCRL, cancer free for 5 years or more, were randomly allocated into two treatment groups: standard of care with bandage treatment and treatment with FIR plus bandage. Variations of fluid, circumference of lymphedematous limbs, serum tumor markers (cancer antigen 125 [CA125]), inguinal-pelvic lymph nodes, vagina, lungs, and adverse reactions were assessed after 1 year. In vitro experiments examined the effects on cell viability, proliferation, apoptosis, and the cell cycle of fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells. Results: The FIR+bandage group showed significantly decreased tissue fluid and reduced limb circumference (p < 0.05) in comparison with the control group at 1 year. There was no increase of serum CA125 in both groups, and no recurrence of neoplasia or lymphadenopathy was detected. No adverse reactions were recorded. In addition, no changes were detected after FIR treatment for fibroblast, A2780, SKOV-3, HELA, and Ishikawa cells in cell viability, proliferation, apoptosis, and cell cycle. Conclusion: FIR can be used to treat patients with GCRL following gynecological cancer treatment. Following clinical and experimental studies, we confirm that FIR is an oncologically safe treatment for lymphedema in gynecological tumor patients.


Asunto(s)
Terapia por Estimulación Eléctrica , Linfedema , Neoplasias Ováricas , Línea Celular Tumoral , Femenino , Humanos , Linfedema/diagnóstico , Linfedema/etiología , Linfedema/terapia , Calidad de Vida
14.
Front Mol Biosci ; 8: 754443, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34926577

RESUMEN

Allogeneic natural killer (aNK) cell adoptive therapy has the potential to dramatically impact clinical outcomes of glioblastoma multiforme (GBM). However, in order to exert therapeutic activity, NK cells require tumor expression of ligands for activating receptors, such as MHC Class I peptide A/B (MICA/B) and ULBPs. Here, we describe the use of a blood-brain barrier (BBB) permissive supramolecular cationic drug vehicle comprising an inhibitor of the chaperone heat shock protein 90 (Hsp90), which sustains a cytotoxic effect on GBM cells, boosts the expression of MICA/B and ULBPs on the residual population, and augments the activity of clinical-grade aNK cells (GTA002). First, we identify Hsp90 mRNA transcription and gain of function as significantly upregulated in GBM compared to other central nervous system tumors. Through a rational chemical design, we optimize a radicicol supramolecular prodrug containing cationic excipients, SCI-101, which displays >2-fold increase in relative BBB penetration compared to less cationic formulations in organoids, in vitro. Using 2D and 3D biological models, we confirm SCI-101 sustains GBM cytotoxicity 72 h after drug removal and induces cell surface MICA/B protein and ULBP mRNA up to 200% in residual tumor cells compared to the naked drug alone without augmenting the shedding of MICA/B, in vitro. Finally, we generate and test the sequential administration of SCI-101 with a clinical aNK cell therapy, GTA002, differentiated and expanded from healthy umbilical cord blood CD34+ hematopoietic stem cells. Using a longitudinal in vitro model, we demonstrate >350% relative cell killing is achieved in SCI-101-treated cell lines compared to vehicle controls. In summary, these data provide a first-of-its-kind BBB-penetrating, long-acting inhibitor of Hsp90 with monotherapy efficacy, which improves response to aNK cells and thus may rapidly alter the treatment paradigm for patients with GBM.

15.
J Plast Reconstr Aesthet Surg ; 74(9): 2341-2348, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33637465

RESUMEN

BACKGROUND: There is currently a lack of patient-reported outcome measures for ear reconstruction. We developed the EAR-Q to measure ear appearance and post-operative adverse effects from the patient perspective. METHODS: Field-test data were collected from children and young adults in eight countries between 13 May 2016 and 12 December 2019. Rasch measurement theory (RMT) analysis was used to refine the scales and to examine their psychometric properties. RESULTS: Participants had microtia (n = 607), prominent ears (n = 145) or another ear condition (n = 111), and provided 960 assessments for the Appearance scale (e.g., size, shape, photos), and 137 assessments for the Adverse Effects scale (e.g., itchy, painful, numb). RMT analysis led to the reduction of each scale to 10-items. Data fit the Rasch model for the Appearance (X2(80) = 90.9, p = 0.19) and Adverse Effects (X2(20) = 24.5, p = 0.22) scales. All items in each scale had ordered thresholds and good item fit. There was no evidence of differential item function for the Appearance scale by age, gender, language, or type of ear condition. Reliability was high for the Appearance scale, with person separation index (PSI) and Cronbach alpha values with and without extremes ≥0.92. Reliability for the Adverse Effects scale was adequate (i.e., PSI and Cronbach alpha values ≥0.71). Higher scores (liked appearance more) correlated with higher scores (better) on Psychological, Social and School scales. INTERPRETATION: The EAR-Q can be used in those 8-29 years of age to understand the patient perspective in clinical practice and research, and in addition, can be used to benchmark outcomes for ear reconstruction internationally.


Asunto(s)
Enfermedades del Oído/psicología , Enfermedades del Oído/cirugía , Medición de Resultados Informados por el Paciente , Procedimientos de Cirugía Plástica , Adolescente , Adulto , Niño , Estética , Femenino , Humanos , Masculino , Psicometría , Reproducibilidad de los Resultados
16.
Sci Rep ; 10(1): 21694, 2020 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-33303965

RESUMEN

Hypertrophic and keloid scars result from abnormal wound healing and can have a variable response to a number of available treatment modalities. The evolution of laser treatments in recent years has shown a wide range of clinical applications including their use in the treatment of scars. We investigated the effectiveness of a 1470 nm diode laser using an intralesional optical fibre delivery device in the treatment of hypertrophic and keloid scars. We evaluated its safety and efficacy as a novel and minimally invasive treatment alternative for scar modulation and volume reduction. A prospective cohort study was performed involving 21 patients with hypertrophic scars (HS) (n = 9) and keloids (n = 12) resulting from various aetiology. Patients were treated with one to three treatment sessions. Comprehensive evaluations were performed using the Vancouver Scar Scale, Doppler ultrasound, Cutometer, Mexameter and PeriCam PSI. Scar thickness was reduced by an average of 0.308 ± 0.138 cm (p < 0.001). In particular the two subgroups showed a significant 27.7% and 28.2% reduction in scar thickness of HS and Keloids, respectively. Scar firmness showed a significant improvement of 1.2% (p < 0.05) for HS, though for keloids this was 0.4% (p = 0.26). Keloids had a significant reduction in pigmentation at 21.3%. Blood perfusion had a significant reduction of 29.6% in HS and 22.7% in Keloids. Overall VSS total score improvement of 42% in the HS and at 37.9% in the Keloid subgroup. No adverse events such as hypo/hyperpigmentation, skin infection, or recurrence were reported. This study shows that the intralesional 1470 nm bare-fibre diode laser significantly improved hypertrophic and keloid scars based on both subjective and objective analyses and supports this type of laser therapy as a safe and effective minimally-invasive treatment option.


Asunto(s)
Cicatriz Hipertrófica/cirugía , Queloide/cirugía , Terapia por Láser/métodos , Láseres de Semiconductores/uso terapéutico , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto Joven
17.
Burns Trauma ; 8: tkaa012, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33335930

RESUMEN

BACKGROUND: Sacral pressure ulcers are associated with high morbidity and, in some cases, result in mortality from severe sepsis. Local flaps are frequently used for reconstruction of stage III and IV pressure ulcers. An ideal flap should be simple to design, have a reliable vascular supply and minimal donor site morbidity. Our study evaluates the use of a bilobed flap based on the superficial branch of the superior gluteal artery or the posterior branch of the fourth lumbar artery to reconstruct the sacral pressure ulcer. CASE PRESENTATION: We performed a retrospective analysis of paraplegic patients with sacral pressure ulcers treated with our bilobed flaps from January 2015 to December 2019. A description of our management, operative protocol, outcome and complications is outlined. Seven paraplegic patients (6 male, 1 female; average age 53.1 years) with sacral pressure ulcers were treated with our bilobed flap based on the superficial branch of the superior gluteal artery or the posterior branch of the fourth lumbar artery. The average size of the pressure ulcers was 7 × 5 cm (range 6.2 × 4.5 cm to 11 × 10 cm). All 7 flaps survived. The patients were followed up for 12 months without significant complications, such as flap necrosis or recurrence. CONCLUSIONS: The superficial branch of the superior gluteal artery or the posterior branch of the fourth lumbar artery reliably supplies the bilobed flap. The superior cluneal nerve can be included in the design. The technique is simple and reliable. It should be included in the reconstructive algorithm for the management of sacral pressure ulcers.

18.
Biomed Res Int ; 2020: 9586806, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33123592

RESUMEN

PURPOSE: The MRI features of epithelioid glioblastoma (eGBM) were analyzed. The apparent diffusion coefficient (ADC), MR perfusion-weighted imaging (PWI), and magnetic resonance spectroscopy (MRS) findings were quantitatively analyzed. METHODS: The MRI images of 8 cases of eGBM were analyzed retrospectively. The location and edge, signal, peritumoral edema, adjacent meningeal invasion, and enhancement of the lesions were observed. The ADC value, relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF), and N-acetylaspartate/acetylcholine (NAA/Cho) value were analyzed. RESULTS: Among the 8 patients, the tumors were mainly located in the temporal lobe (n = 3), frontal lobe (n = 3), and parietal lobe (n = 2). The lesion boundary was clear in 6 cases and unclear in 2. The lesions were superficial in 5 cases and in the deep white matter in 3. Internal hemorrhage was observed in 4 cases. There was cystic necrosis in 7 cases, and only 1 case was solid without cystic necrosis. There was no edema around the lesion in 1 case, severe edema in 5, and moderate edema in 2. In 4 cases, the adjacent meninges were involved, and in 1 case, the ependyma was involved. Two patients developed leptomeningeal metastasis within 2 months after the operation. The average ADC value of the tumor parenchyma among all 8 patients was7.15 × 10-4 mm2/s,which was 17.6% lower than that of the contralateral side. The Cho/NAA metabolite ratio was 5.27 and 0.81 in the lesions of 2 patients. The rCBV was 3.51 ml/100 g and 3.32 ml/100 g of lesions in 2 patients; these values were 36% and 29% higher, respectively, than those of the contralateral side. The rCBF was 31.5 ml/100 g/min and 82.1 ml/100 g/min of lesions in two patients; these values were 49% and 203% higher, respectively, than those of the contralateral side. CONCLUSION: eGBM characteristics include a superficial location, easy cyst degeneration, easy necrosis and hemorrhage, and clear boundaries. It easily invades adjacent meninges and shows cerebrospinal fluid dissemination and metastasis. Combining new MR techniques, such as ADC values, PWI, and MRS, could be helpful for improving diagnostic accuracy.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/patología , Células Epitelioides/patología , Glioblastoma/diagnóstico , Glioblastoma/patología , Adulto , Anciano , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Neoplasias Encefálicas/metabolismo , Circulación Cerebrovascular/fisiología , Colina/metabolismo , Creatina/metabolismo , Imagen de Difusión por Resonancia Magnética/métodos , Edema/metabolismo , Edema/patología , Células Epitelioides/metabolismo , Femenino , Glioblastoma/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia/diagnóstico , Metástasis de la Neoplasia/patología
19.
Br J Radiol ; 93(1115): 20200287, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32822542

RESUMEN

OBJECTIVES: To investigate the ability of radiomic signatures based on MRI to evaluate the response and efficiency of neoadjuvant chemotherapy (NAC) for treating breast cancers. METHODS: 152 patients were included in this study at our institution between March 2017 and September 2019. All patients with breast cancer underwent a preoperative breast MRI and the Miller-Payne grading system was applied to evaluate response to NAC. Quantitative parameters were compared between patients with sensitive and insensitive responses to NAC and between those with pathological complete responses (pCR) and non-pCR. Four radiomic signatures were built based on T2W imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging and their combination, and radiomics scores (Rad-score) were calculated. The combination of the clinical factors and Rad-scores created a nomogram model. Multivariate logistic regression was performed to assess the association between MRI features and independent clinical risk factors. RESULTS: 20 features and 18 features were selected to build the radiomic signature for evaluating sensitivity and the possibility of pCR, respectively. The combined radiomic signature and nomogram model showed a similar discrimination in the training (AUC 0.91, 0.92, 95% confidence interval [CI], 0.85-0.96, 0.86-0.98) and validation (AUC 0.93, 0.91, 95% CI, 0.86-1.00, 0.82-1.00) sets. The clinical factor model exhibited reduced performance (AUC 0.74, 0.64, 95% CI, 0.64-0.84, 0.46-0.82) in terms of NAC sensitivity and pCR. CONCLUSIONS: The combined radiomic signature and nomogram model exhibited potential predictive power for predicting effective NAC treatment which can aid in the prognosis and guidance of treatment regimens. ADVANCES IN KNOWLEDGE: Identifying a means of assessing the efficacy of NAC before surgery can guide follow-up treatment and avoid chemotherapy-induced toxicity.


Asunto(s)
Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/tratamiento farmacológico , Imágenes de Resonancia Magnética Multiparamétrica , Terapia Neoadyuvante/métodos , Nomogramas , Adulto , Anciano , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Área Bajo la Curva , Neoplasias de la Mama/química , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Intervalos de Confianza , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Cuidados Preoperatorios/métodos , Estudios Retrospectivos , Resultado del Tratamiento
20.
Biofabrication ; 12(4): 045018, 2020 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-32650325

RESUMEN

Technology of tissue-engineering advanced rapidly in the last decade and motivated numerous studies in cell-engineering and biofabrication. Three-dimensional (3D) tissue-engineering scaffolds play a critical role in this field, as the scaffolds provide the biomimetic microenvironments that could stimulate desired cell behaviors for regeneration. However, despite many achievements, the fabrication of 3D scaffold remains challenging due to the difficulty of encapsulating cells in 3D scaffolds, controlling cell-cell organization in 3D, and being adapted by users unfamiliar with 3D biofabrication. In this study, we circumvent these obstacles by creating a four-dimensional (4D) inkjet-printing platform. This platform produces micropatterns that self-fold into a 3D scaffold. Seeding live cells uniformly onto the micropatterns before self-folding leads to cell-encapsulating 3D scaffolds with layer-wise cell-cell organization. Photo-crosslinkable biomaterial-inks of distinct swelling rates were synthesized from gelatin, and the biomaterial-inks were patterned by a customized high-precision inkjet-printer into bilayer micropatterns that were capable of self-folding into 3D microstructures. A mathematical model was developed to help design self-folding and to aid the understanding of the self-folding mechanism. Human umbilical vein endothelial cells (HUVECs) were embedded in self-folded microtubes to mimic microvessels. HUVECs in the microtube spread, proliferated, showed high cell viability, and engrafted on the microtube's inner wall mimicking the native endothelial cells. For physician and biologist end-users, this 4D printing method provides an easy-to-use platform that supports standard two-dimensional cell-seeding protocol while enabling the users to customize 3D cellularized scaffold as desired. This work demonstrated 4D printing as a promising tool for tissue-engineering applications.


Asunto(s)
Células Inmovilizadas/citología , Impresión Tridimensional , Ingeniería de Tejidos , Andamios del Tejido/química , Materiales Biocompatibles/química , Supervivencia Celular , Preparaciones de Acción Retardada , Células Endoteliales de la Vena Umbilical Humana/citología , Humanos , Tinta , Modelos Teóricos , Temperatura
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